An examination of two different approaches for the study of femoral neck fracture: Towards a more relevant rodent model

Abstract

Femoral neck fractures are a massive personal and health programme burden. Methods to study femoral neck strength, across its combined trabecular and cortical components are therefore essential. Rodent ovariectomy-induced osteoporosis models are commonly coupled with ex vivo 3-/4-point bending methods to measure changes in femoral cortical diaphysis. The loading direction used to assess these properties are often non-physiologic and, moreover, these ovariectomy models are linked to marked weight gain that can influence the biomechanical properties. Herein, we explore whether more physiological axial ex vivo loading protocols applied to femoral neck samples of ovariectomised (OVX) rodents provide anatomically-relevant models for the assessment of strength. We examine the use of mouse and rat femurs, loaded in constrained and unconstrained configuration, respectively, and explore whether weight-correction increases their utility. Accordingly, the mid-shaft of the proximal half of femurs from OVX and sham-operated (Sham) mice was methacrylate-anchored and the head loaded parallel to the diaphysis (constrained). Alternatively, femurs from OVX and Sham rats were isolated intact and axially-loaded through hip and knee joint articular surfaces (unconstrained). Yield displacement, stiffness, maximum load and resilience were measured and fracture pattern classified; effects of body weight-correction via a linear regression method or simple division were assessed. Our data reveal significant deficiencies in biomechanical properties in OVX mouse femurs loaded in constrained configuration, only after weight-correction by linear regression. In addition, evaluation of rat femur biomechanics in unconstrained loading demonstrated greater variation and that weight-correction by simple division improved scope to reveal significant OVX impact. We conclude that greater femoral neck fracture susceptibility can indeed be measured in OVX rodents as long as multiple biomechanical parameters are reported, care is taken in choosing the method for assessing load-bearing strength and weight-correction applied. These studies advance the establishment of more relevant rodent models for the study of femoral neck fracture.